Apparatus, method and system for selectively affecting and/or killing a virus

ABSTRACT

Certain exemplary embodiments of the present disclosure can provide an apparatus and method for generating at least one radiation can be provided. The exemplary apparatus and/or method can selectively kill and/or affect at least one virus. For example, a radiation source first arrangement can be provided which is configured to generate at least one radiation having one or more wavelengths provided in a range of about 200 nanometers (nm) to about 230 nm, and at least one second arrangement can be provided which is configured to prevent the at least one radiation from having any wavelength that is outside of the range can be provided or which can be substantially harmful to cells of the body.

CROSS-REFERENCE TO PRIOR APPLICATION(S)

This application relates to, and claims priority from, U.S. ProvisionalApplication No. 62/170,203, filed on Jun. 3, 2015, the entire disclosureof which is incorporated herein by reference in its entirety. Thisapplication also relates to U.S. Provisional Application No. 61/450,038,filed on Mar. 7, 2011, International Patent Application No.PCT/US2012/027963 filed Mar. 7, 2012, and U.S. patent application Ser.No. 14/021,631, filed on Sep. 9, 2013, the entire disclosures of whichare hereby incorporated by reference in their entirety.

FIELD OF THE DISCLOSURE

Exemplary embodiments of the present disclosure relate to selectivelyaffecting and/or killing a virus, and more specifically to exemplaryapparatuses, methods and systems which can use an ultraviolet radiationto selectively affect and/or kill a virus while not harming human cells.

BACKGROUND INFORMATION

There may be a need to address at least some of the deficiencies ofexisting conventional systems and methods for killing viruses, which canovercome deficiencies in present systems.

SUMMARY OF EXEMPLARY EMBODIMENTS

Accordingly, exemplary embodiments of the exemplary apparatuses, methodsand systems can be provided that can address at least some of suchdeficiencies of present systems and methods for killing viruses. Forexample, exemplary embodiments of the exemplary apparatuses, methods andsystems can use an ultraviolet (“UV”) radiation to selectively affectand/or kill bacteria or viruses while not harming human cells.

In particular, in certain exemplary embodiments of the presentdisclosure, a UV irradiator, for example, an excilamp, can be providedwhich can affect and/or kill bacteria or viruses, without being harmfulto human cells. The exemplary system, method and apparatus takes intoconsideration the fact that bacteria and viruses are typicallyphysically much smaller than human cells, and thus, an appropriatelychosen UV wavelength (e.g., around 207 nm to 222 nm) preferablypenetrates and kills bacteria and viruses, but preferably would not beable to penetrate into the biologically sensitive nucleus of humancells. Irradiating a wound with this exemplary tailored UV radiation,for example, can therefore provide the advantages of UV bacterial andviral sterilization, while being safe for a patient and staff, andpreferably not requiring protective clothing/hoods/eye shields, or thelike. According to another exemplary embodiment of the presentdisclosure, the room air, or surfaces (e.g., walls, floors, ceiling,countertops, furniture, fixtures, etc.) can be exposed to this exemplaryUV lamp in hospital environments.

According to further exemplary embodiments of the present disclosure, itcan be possible to provide exemplary UV lamps that can emit at a singlewavelength, in contrast to standard mercury UV lamps which typicallyemit over a wide range of wavelengths. The exemplary lamps can includeUV radiation emitted from an excited molecule complex (e.g., anexciplex, such as either krypton-bromine or krypton-chlorine), calledexcilamps, and can be modified in accordance with certain exemplaryembodiments of the present disclosure to produce UV radiation having asingle wavelength, thus, facilitating modifying the UV radiation to haveenough energy to penetrate and kill bacteria and viruses, but not enoughrange to penetrate to the nucleus of human cells. This can be performedbased on certain exemplary embodiments, for example, using one or moremodulators, wavelength-effecting masks, etc.

An exemplary excilamp wound irradiation can facilitate a practical andinexpensive approach to significantly reducing viral transmissionsthrough airborne or surface contact. According to certain exemplaryembodiments of the present disclosure, a UV radiation at approximately207 nm to about 222 nm can be provided, for example, that candifferentially damage and/or kill methicillin-resistant Staphylococcusaureus (“MRSA”), relative to human cells. Although a conventionalgermicidal UV lamp can be approximately equally efficient at killingMRSA and human cells, by contrast, the exemplary 207 to 222 nm UVwavelength from excilamps can be approximately 5,000 times moreefficient at killing MRSA relative to killing human cells.

According to certain exemplary embodiments of the present disclosure, anapparatus and method for generating a radiation(s) can be provided.According to certain exemplary embodiments, the exemplary apparatusand/or method can selectively kill and/or affect bacteria and/orvirus(es) on a surface, or in an aerosol. For example, a radiationsource first arrangement configured to generate radiation(s) having oneor more wavelengths provided in a range of about 190 nanometers (“nm”)to about 230 nm, and second arrangement(s) configured to substantiallyprevent the radiation(s) from having any wavelength that can be outsideof the range can be provided. The radiation can be configured toselectively affect or destroy the bacteria and/or virus(es) on a surfaceor in an aerosol, while substantially avoiding harm to cells of thebody. The radiation source can include, for example, an excilamp, suchas a krypton-bromine lamp or a krypton-chlorine lamp. Additionally, theradiation source first arrangement can be further configured to generatethe radiation(s) having a single wavelength provided in the range, andthe second arrangement(s) can be further configured to prevent theradiation from having any wavelength other than the single wavelength.The single wavelength can be about 207 nm, and/or about 222 nm. Further,the second arrangement(s) can include a chemical filter or a dielectricfilter.

In some exemplary embodiments according to the present disclosure, thesingle wavelength can be 200 nm, 201 nm, 202 nm, 203 nm, 204 nm, 205 nm,206 nm, 208 nm, 209 nm, 210 nm, 211 nm, 212 nm, 213 nm or 214 nm. Incertain exemplary embodiments of the present disclosure, the singlewavelength can be 215 nm, 216 nm, 217 nm, 218 nm, 219 nm, 220 nm, 221nm, 223 nm, 224 nm, 225 nm, 226 nm, 227 nm, 228 nm, 229 nm or 230 nm.The wavelengths can include a range of about 190-194 nm, 195-199 nm,200-204 nm, 205-209 nm, 210-214 nm, 215-218 nm, 219-223 nm or 224-230nm. The virus can have a susceptibility parameter of Z=0.42 m2/J.

The surface can include an animate surface, which can include skin of aperson(s) a cornea of a person(s) or mucous of a person(s). The surfacecan also include an inanimate surface, which can include a fomitesurface(s).

According to yet another exemplary embodiment, systems and methods canbe provided for generating radiation(s). For example, for example, usinga radiation source first arrangement or another arrangement, it can bepossible to generate the radiation(s) having one or more wavelengthsprovided in a range of about 190 nanometers (“nm”) to about 230 nm.Further, it can be possible to, using second arrangement(s) and/or thesame arrangement, to substantially prevent the radiation(s) from havingany wavelength that can be outside of the range.

The radiation(s) can be configured to selectively affect or destroy thebacteria and/or the virus(es) on a surface, while substantially avoidingharming to any of cells of the body. The radiation source can include anexcilamp, a krypton-bromine lamp and/or a krypton-chlorine lamp. Theradiation source first arrangement can be further configured to generatethe radiation(s) having a single wavelength provided in the range, andthe second arrangement(s) can be further configured to prevent theradiation(s) from having any wavelength other than the singlewavelength. The single wavelength can be about 206 nm, 207 nm, and/or222 nm. The second arrangement(s) can include a chemical filter and/or adielectric filter.

These and other objects, features and advantages of the presentdisclosure will become apparent upon reading the following detaileddescription of embodiments of the present disclosure in conjunction withthe appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the present disclosure willbecome apparent from the following detailed description taken inconjunction with the accompanying Figures showing illustrativeembodiments of the present disclosure, in which:

FIG. 1 is an exemplary graph of an exemplary spectrum of UV wavelengthsgenerated by a typical mercury UV lamp;

FIG. 2 is an exemplary illustration of an exemplary penetration of lowwavelength UV radiation with respect to human cells and bacteria inaccordance with an exemplary embodiment of the present disclosure;

FIG. 3 is an exemplary illustration of an exemplary excilamp which canprovide the UV radiation at a single wavelength, or in a particularrange of wavelengths, in accordance with an exemplary embodiment of thepresent disclosure;

FIG. 4 is an exemplary graph of the exemplary spectral distributions ofthe UV radiation generated by excilamps in accordance with certainexemplary embodiments of the present disclosure;

FIG. 5 is an exemplary block diagram of an apparatus according toparticular exemplary embodiments of the present disclosure;

FIGS. 6A and 6B are exemplary spectral graphs of exemplary excilampsaccording to certain exemplary embodiments of the present disclosure;

FIG. 7 is an exemplary graph of human cell survival with respect to UVfluence, according to certain exemplary embodiments of the presentdisclosure;

FIG. 8 is an exemplary graph of MRSA survival with respect to anexcilamp fluence according to certain exemplary embodiments of thepresent disclosure;

FIG. 9 is an exemplary graph illustrating mean wavelength-dependent UVabsorbance coefficients, averaged over measurements for 8 commonproteins, according to an exemplary embodiment of the presentdisclosure;

FIG. 10 is an exemplary graph illustrating measured non-filtered andfiltered UV spectra for the exemplary 207 nm KrBr excimer lamp accordingto an exemplary embodiment of the present disclosure;

FIG. 11A is an exemplary graph illustrating a comparison of killing orotherwise affecting of MRSA cells and AG1522 normal human fibroblastcells using a conventional germicidal UV lamp;

FIG. 11B is an exemplary graph illustrating a comparison of killing orotherwise affecting of MRSA cells and AG1522 normal human fibroblastcells using the exemplary 207 nm excimer lamp according to an exemplaryembodiment of the present disclosure;

FIG. 12A is an exemplary graph illustrating the effect of a conventionalgermicidal UV lamp and an exemplary filtered 207 nm UV lamp on theproduction of cyclobutane pyrimidine dimer in human skin model;

FIG. 12B is an exemplary graph illustrating the effect of a conventionalgermicidal UV lamp and an exemplary filtered 207 nm UV lamp on theproduction of pyrimidine-pyrimidone 6-4 photoproducts (e.g., 6-4 PP) inhuman skin model;

FIG. 13A is a set of exemplary cross-sectional images from the exemplaryin-vivo safety preliminary studies in hairless mouse skin, comparing theeffects of 207 nm UV exposure with the same fluence of 254 nmconventional germicidal lamp exposure;

FIG. 13B is an exemplary chart illustrating a percent of epidermal cellswith premutagenic lesions for particular UV wavelengths;

FIG. 14 is an exemplary photograph of an exemplary aerosol UV exposurechamber, inside a BSL-2 cabinet, according to an exemplary embodiment ofthe present disclosure;

FIG. 15 is an exemplary photograph of a mouse-irradiation box for UVexposures according to an exemplary embodiment of the presentdisclosure;

FIG. 16 is an exemplary flow diagram illustrating mouse distribution forbiological assays according to an exemplary embodiment of the presentdisclosure;

FIG. 17 is an exemplary graph illustrating exemplary H1N1 survivalresults from a conventional germicidal lamp compared to the H1N1survival results from the exemplary system, method andcomputer-accessible medium according to an exemplary embodiment of thepresent disclosure; and

FIG. 18 is an exemplary flow diagram of an exemplary method forselectively killing or affecting a virus according to an exemplaryembodiment of the present disclosure.

Throughout the drawings, the same reference numerals and characters,unless otherwise stated, are used to denote like features, elements,components or portions of the illustrated embodiments. Moreover, whilethe present disclosure will now be described in detail with reference tothe figures, it is done so in connection with the illustrativeembodiments and is not limited by the particular embodiments illustratedin the figures and the accompanying claims.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

Ultra violet (“UV”) radiations of different wavelengths can havedifferent abilities to penetrate into cells. Typically, the higher thewavelength, the more penetrating the radiation, and the lower thewavelength, the less penetrating the radiation. For example, UVradiation with a low wavelength of about 200 nm, while able to passthrough water quite efficiently, can be heavily absorbed in the outerpart of a human cell (e.g., the cytoplasm, see, for example, anexemplary diagram in FIG. 2), and may not have enough energy to reachthe biologically sensitive cell nucleus. FIG. 1 shows a graph of anexemplary spectrum of UV wavelengths generated by a typical mercury UVlamp.

The limited penetrating ability of approximately 200 nm UV radiation canbe used for killing bacteria or viruses, as shown in the exemplarydiagram of FIG. 2, because bacteria or viruses are typically physicallyfar smaller than human cells. Specifically, a typical bacterial cell isless than about 1 micrometer (“μm”) in diameter, and a typical virus canvary from about 20 nm to about 400 nm, whereas human cells are typicallyabout 10 to 30 μm across, depending on their type and location. Thus,the exemplary system, method and computer-accessible medium, accordingto an exemplary embodiment of the present disclosure, can be used tominimize airborne and surface-based transmissions of common viruses,such as H1N1, SARS-CoV and MERS-CoV, and of extremely dangerous viruses,including Dengue and Ebola, without harming human cells.

In particular, FIG. 2 shows a diagram of a typical human cell nucleushaving a spherical geometry 202 or a flattened geometry 204,illustrating the penetration into a human cell of UV radiation with awavelength of around 200 nm. As shown in FIG. 2, effectively no UVradiation of this wavelength preferably reaches the cell nucleus 202 and204, which contains the radiation-sensitive DNA. Accordingly, UVradiation of this wavelength would typically not be harmful to humancells or to humans. In addition, there can be a biological reason why UVwith a wavelength around 200 nm will typically not be harmful to humans.At about 185 nm and below, UV radiation can be very efficiently absorbedby oxygen, producing ozone and oxidative damage. Above about 240 nm, UVradiation can be very efficient at producing oxidative DNA base damage.(See, e.g., References 96 and 97). Thus, a 200 nm wavelength UVradiation can be in a narrow UV “safety window”. In contrast, becauseviruses are typically physically much smaller in size than human cells,UV radiation with a wavelength around 200 nm can penetrate through, andtherefore kill, viruses.

According to exemplary embodiments of the present disclosure, it can bepossible to utilize one or more UV excilamps, or one or more UV lasersor other coherent light sources, which, in contrast to standard UVlamps, can produce UV radiation at a specific wavelength—for example,around 200 nm. UV radiation around such exemplary wavelength (e.g., asingle wavelength or in a range of certain wavelengths as describedherein) can penetrate and kill bacteria, but preferably would notpenetrate into the nucleus of human cells, and thus, can be expected tobe safe for both patient and staff.

Exemplary Excilamp UV Irradiator

The exemplary excilamp can utilize certain exemplary concepts which weredeveloped at the Institute of High Current Electronics (“IHCE”). (See,e.g., Reference 11). Additional exemplary excilamps that can be utilizedwith the exemplary embodiments of the present disclosure may beavailable from Heraeus Noblelight in Germany. The IHCE lamps, anexemplary embodiment of such lamp 302 is shown in the diagram of FIG. 3,can be small, rugged, cost approximately $1,000, and can be made toproduce a variety of single wavelength UV radiations. Additionally, afilter 304 can be used to filter any UV radiation emitted from a side oflamp 302. Based on the considerations above, exemplary embodiments ofthe present disclosure can use, for example, a krypton-bromine lamp(e.g., an excilamp), which can produce UV radiation at about 207 nm, ora krypton-chlorine lamp (see, e.g., FIG. 3), which can produce UVradiation at about 222 nm. The exemplary spectra of these lamps areshown in the graph of FIG. 4. As shown therein, a spectral distribution402 was produced by a krypton-bromine lamp, and spectral distribution404 was produced by a krypton-chlorine lamp. Additionally, according tofurther exemplary embodiments of the present disclosure, certainexemplary features can be included (e.g., spectrum filtering elementssuch as multilayer dielectric filters or chemical filters) to removeunwanted wavelengths, or those wavelengths that can be outside of thepreferable range of wavelengths. For example, absorption and/orreflective elements can be provided between the lamp and the irradiatedsurface to filter unwanted wavelengths, such as, for example, aband-pass filter, a long-wavelength blocking filter. In one exemplaryembodiment, the absorptive material can be fluorescent, such that itemits visible light when it absorbs UV radiation to provide anindication that the lamp is operating. Alternatively, or in addition,other gases can be added to the lamp to suppress unwanted wavelengths.For example, adding argon to the krypton-bromine lamp can suppressgeneration of the 228 nm UV radiation.

The typical power density output of the air-cooled excilamps can beabout 7.5 to about 20 mW/cm², although higher power density can beobtained in a water-cooled system. At about 20 mW/cm², only a fewseconds of exposure, or even only 1 second of exposure, can deliverabout 20 mJ/cm², which can be a typical bactericidal dose.

Exemplary embodiments of the present disclosure can provide an excilamp,emitting about a 207 nm or about a 222 nm single wavelength UVradiation, to differentially kill bacteria while sparing adjacent humancells. Further, the wavelength(s) of the UV radiation, according tofurther exemplary embodiments of the present disclosure, can be in therange of about 190 nm to about 230 nm, or in the range of about 200 nmto about 230 nm. Exemplary experiments implementing embodiments of thepresent disclosure can include: an in-vitro (e.g., laboratory) 3-D humanskin system (see, e.g., References 49 and 98), a nude mouse model forin-vivo safety standards, and/or an in-vitro wound infection model.(See, e.g., Reference 99).

In an exemplary experiment implementing certain exemplary embodiments ofthe present disclosure, an exemplary test bench was developed forgathering, for example, exemplary preliminary sterilization results fromexemplary UV radiation sources. For example, the exemplary test benchcan include: (i) a light-tight box, (ii) a shutter control, (iii) afilter holder and (iv) adjustable exposure parameters for time, distanceand wavelength (e.g., 207 nm KrBr excilamp, 222 nm, KrCl excilamp, and254 nm standard germicidal lamp). Additionally, exemplary custom filterscan be designed to eliminate higher-wavelength components in theexcilamp emission spectra to provide optimal single-wavelength exposure.A UV spectrometer and deuterium lamp (e.g., for equipment calibration)can be used to validate the filter effectiveness, as shown, for example,the graphs shown in FIGS. 6A and 6B, which illustrate the normalizedspectra comparing excilamp emission (e.g., elements 602 a and 602 b)with filtered excilamp emission (e.g., elements 604 a and 604 b) forboth KrBr and KrCl excilamps. This exemplary test bench facilitated, forexample, a generation of biological findings of filtered excilampexposure to both bacteria and healthy human cells, which are describedbelow. In turn, the exemplary biological testing experience has provideddetails regarding exemplary parameters for developing filtered KrBr andKrCl excilamps into optimal devices for clinical applications.

Exemplary Biological Results

Described below are certain exemplary experiments implementing certainexemplary embodiments of the present disclosure. The exemplaryexperiments investigated, for example, whether UV radiation fromexemplary filtered excilamps can be effective at killing bacteria whilesparing normal human cells.

In the exemplary experiment, human fibroblasts were, for example,exposed to about 3 mJ/cm² from a standard germicidal UV lamp (e.g.,about 254 nm), and their survival was less than about 10⁻⁴. By contrast,when they were exposed to fluences as high as 150 mJ/cm² from theexemplary filtered KrBr or KrCl excilamp (e.g., about 207 and about 222nm, respectively), their survival was in the range from about 1 to about10⁻¹. (See, e.g., graph shown in FIG. 7). Indeed, FIG. 7 shows anexemplary graph indicating a clonogenic survival of normal human skinfibroblasts (e.g., AG1522) exposed to UV radiation from exemplaryfiltered KrBr (e.g., about 207 nm, element 705) or KrCl (e.g., about 222nm, element 710) excilamps, or from a conventional germicidal lamp(e.g., about 254 nm, element 715).

In the exemplary experiment, bactericidal killing efficacy of theexemplary excilamps was tested, for example, on methicillin resistantStaphylococcus aureus (“MRSA”). MRSA can be the cause of about 25% ofsurgical site infection, and can be associated with approximately 20,000deaths per year in the United States; mostly healthcare related. MRSAand antibiotic-susceptible S. aureus are typically equally susceptibleto UV radiation from conventional germicidal lamps. (See, e.g.,Reference 2). The exemplary results are shown, for example, in the chartof FIG. 8, which shows that at an excilamp fluence of about 100 mJ/cm²,a MRSA survival level of 10⁻⁴ can be achieved. For example, FIG. 8 showsan exemplary graph of MRSA (e.g., strain US300) inactivation afterexposure to UV radiation from the exemplary filtered KrBr excilamp(e.g., about 207 nm, element 805) or a KrCl excilamp (e.g., about 222nm, element 810).

Comparing the exemplary results in FIGS. 7 and 8, the exemplary filteredexcilamp UV radiation at about 207 nm and at about 222 nm candifferentially effect and/or kill MRSA relative to the human cells. Forexample, at exemplary filtered excilamp fluences of about 100 mJ/cm²,the survival level of human cells can be, for example, in the range ofabout 0.1 to 1, while the survival level of MRSA can be in the range ofabout 10⁻⁴. Such exemplary findings are in considerable contrast to thesituation for convention germicidal UV lamps (“GUVL”), which can beroughly equally efficient at killing bacteria and human cells. Forexample, for a conventional germicidal UV lamp, at a UV fluence forwhich a GUVL can produce a bacterial survival of 10⁻⁴, the human cellsurvival from the GUVL can be about 0.3×10⁻⁴, a human cell survivaladvantage of 0.3. With the exemplary excilamp at about 207 or about 222nm, at a UV fluence for which the exemplary 207 or 222 nm filteredexcilamp can produce a bacterial survival of 10⁻⁴, the human cellsurvival by the exemplary filtered excilamps can be in the range ofabout 0.1 to 1, a human cell survival advantage in the range of 5,000.

FIG. 5 shows an exemplary block diagram of an exemplary embodiment of asystem according to the present disclosure. For example, exemplaryprocedures in accordance with the present disclosure described hereincan be performed by or controlled using a UV generation source 580and/or hardware processing arrangement and/or a computing arrangement510, separately and in conjunction with one another. Such exemplaryprocessing/computing arrangement 510 can be, for example, entirely or apart of, or include, but not limited to, a computer/processor 520 thatcan include, for example, one or more microprocessors, and useinstructions stored on a computer-accessible medium (e.g., RAM, ROM,hard drive, or other storage device).

As shown in FIG. 5, for example, a computer-accessible medium 530 (e.g.,as described herein above, a storage device such as a hard disk, floppydisk, memory stick, CD-ROM, RAM, ROM, etc., or a collection thereof) canbe provided (e.g., in communication with the processing arrangement510). The computer-accessible medium 530 can contain executableinstructions 540 thereon. In addition or alternatively, a storagearrangement 550 can be provided separately from the computer-accessiblemedium 530, which can provide the instructions to the processingarrangement 510 so as to configure the processing arrangement to executecertain exemplary procedures, processes and methods, as described hereinabove, for example.

Further, the exemplary processing arrangement 510 can be provided withor include an input/output arrangement 570, which can include, forexample, a wired network, a wireless network, the internet, an intranet,a data collection probe, a sensor, etc. As shown in FIG. 5, theexemplary processing arrangement 510 can be in communication with anexemplary display arrangement 560, which, according to certain exemplaryembodiments of the present disclosure, can be a touch-screen configuredfor inputting information to the processing arrangement in addition tooutputting information from the processing arrangement, for example.Further, the exemplary display 560 and/or a storage arrangement 550 canbe used to display and/or store data in a user-accessible format and/oruser-readable format.

Exemplary Safety Studies in Hairless Mice and in Pigs

To determine the 207 nm UV radiation safety in vivo, SKH-1 hairless miceand pigs can be exposed to this UV wavelength radiation, and a varietyof biological damage endpoints can be assessed. Positive control can bethe same-dose exposure as a conventional 254 nm germicidal UV lamp.Negative controls can receive no UV radiation exposure. The endpointscan be physiological endpoints (e.g., skin edema and erythema),epidermal immunohistochemical and molecular endpoints, as well ascataractogenesis.

Exemplary Efficacy Studies for MRSA Killing in a Hairless Mouse SkinWound Model and in a Pig Skin Wound Model

The efficacy of 207 nm radiation (e.g., light) can be assessed with thegoal of using it to prevent SSI by continuous exposure of the woundduring surgery. For example, a liquid suspension containing live MRSAcan be applied to the skin on the backs of SKH-1 hairless mice and ofpigs, followed by wound induction and suturing. One set of wound sitescan be treated with topical antibiotics (e.g., positive control),another set can remain untreated (e.g., negative control), and a thirdset can be exposed to 207 nm radiation. Staged inspections of wounds forinfection can be undertaken using objective wound assessment criteria.

Exemplary Efficacy Studies for Inactivation of Influenza Virus onSurfaces and in Aerosols

Far-UVC light (e.g., light of about 190 nm to about 230 nm, or light ofabout 200 nm to about 230 nm) can kill or otherwise damage bacteria asefficiently as a conventional germicidal lamps. (See, e.g., Reference94). In addition, UV radiation emitted in the same or similar range, by,for example, a KrCl excilamp (e.g., at about 222 nm), or a laser lightsource (e.g., at about 222 nm), can be similarly effective at killingand/or damaging viruses.

The antiviral efficacy of 222 nm UV radiation can be assessed ascompared with 254 nm UV radiation from a conventional germicidal lamp,for the H1N1 influenza virus. Fluence-dependent virus inactivationdeterminations can be done for influenza viruses, Ebola, SARS and/orMERS on surfaces, such as fomite surfaces, which are surfaces capable ofcarrying infectious organisms, and subsequently for influenza virus inaerosols, using the exemplary bench top aerosol UV irradiation chamber.

UV radiation is a well-established highly-efficient anti-microbialmodality, effective both against bacteria and viruses. However it isgenerally not practical to use UV sterilization in scenarios wherepeople can be present, because it can be a human health hazard, beingboth carcinogenic and cataractogenic. Based on biophysical principles,the exemplary system, method and computer-accessible medium can includea far-UVC light source (e.g., at approximately 207 nm) from, for examplea KrBr excimer lamp, a laser light source or a coherent light source(e.g., a light source having the same phase, the same polarizationand/or the same direction), that has the anti-microbial advantages—bothfor bacteria and viruses—compared to conventional UV germicidal lamps,and without the corresponding human safety hazards.

There can potentially be significant applications both for bacterialcontrol, and also for preventing surface and airborne spread of avariety of viruses (e.g., on animate surfaces or inanimate surfaces,including fomite surfaces which are surfaces capable of carryinginfectious organisms). One exemplary advantage can be that theUV-mediated bacterial killing can be independent of drug resistance(see, e.g., References 2 and 3), using the exemplary system, method, andcomputer-accessible medium, according to an exemplary embodiment of thepresent disclosure.

The biophysical considerations on which the exemplary system, method andcomputer-accessible medium can be based can be as follows. For example,UV radiation at a wavelength of around 200 nm can be very stronglyabsorbed by proteins (e.g., particularly through the peptide bond) andother biomolecules (see, e.g., References 4 and 5), so its ability topenetrate biological material can be very limited. Thus, for example,the intensity of about 207-nm UV radiation can be reduced by half inonly about 0.3 μm of tissue, compared with about 3 μm at 250 nm and muchlonger distances for higher UV radiation wavelengths. (See, e.g.,References 6 and 7). This phenomenon is shown in the graph of FIG. 9. Incontrast, about 207 nm UV radiation may only be minimally absorbed inpure water. (See, e.g., Reference 8).

The very short range in biological material of about 207-nm UV radiationmeans that, while it can penetrate and kill both bacteria and viruses onsurfaces or in aerosols (e.g., bacteria, viruses, and aerosols are alltypically less than 1 μm in diameter), it cannot penetrate througheither the human stratum corneum (e.g., the outer dead-cell skin layer,which in humans can be 5-20 μm thick (see, e.g., Reference 9)), nor theocular cornea, nor even the cytoplasm of individual human cells (e.g.,most human cells range in diameter from 10-25 μm (see, e.g., Reference10), and the layer thickness of the cytoplasm about the nucleus can bebetween about 1 micron to about 4.5 microns as shown in FIG. 2).

The exemplary system, method and computer-accessible medium, accordingto an exemplary embodiment of the present disclosure, can use excimerlamps, often called excilamps that primarily emit a single UV wavelengthfrom a specific excited molecule complex. (See, e.g., Reference 11 and12). Excilamps that emit in the wavelength region of interest, haverecently become commercially available, and contain, for instance, akrypton-bromine mixture, which can produce high-intensity far-UVCradiation at about 207 nm. (See, e.g., Reference 11). Excilamps can besmall, rugged, inexpensive, sufficiently intense, and long-lived (e.g.,approximately 10,000 hours). (See, e.g., Reference 11, 13 and 14). Theseexcilamps can also emit a low level of higher wavelength UV radiation,which would be unacceptable for the exemplary applications. However, UVradiation filters (e.g., bandpass filters) can be used to eliminateharmful wavelength.

Exemplary Reduction of Surgical Site Infections:

Between about 0.5% and about 10% of all clean surgeries in the UnitedStates, corresponding to about 275,000 patients per year, can result inSSI. (See, e.g., References 15-17). Patients who develop SSI can beabout 60% more likely to spend time in an ICU, can be 5 times as likelyto be readmitted, have a mortality rate twice that of non-infectedpatients, have an average of 7 days additional length of hospital stay(see, e.g., Reference 18), and have roughly double the total healthcarecosts compared with patients without SSI. (See, e.g., Reference 19). Theannual number of deaths in the United States attributed to SSI has beenestimated at about 8,200 (see, e.g., Reference 16), with annual patienthospital costs between about $3 billion and about $10 billion. (See,e.g., Reference 20).

There can be potentially two different bacterial pathways to surgicalsite infection: (i) first internal, largely through the bloodstream, and(ii) second external, largely through airborne transmission. Therelative importance of these two pathways can depend on the type ofsurgery in question, but current evidence suggests that the majority ofSSI result from bacteria alighting directly onto the surgical wound fromthe air. Evidence for the dominance of an airborne route comes fromcorrelations between the density of airborne bacteria and postoperativesepsis rates. (See, e.g., References 21 and 22). Evidence for thesignificance of airborne bacteria alighting directly on the surgicalwound comes, for example, from studies of conventional UV lampsspecifically directed over the surgical site (see, e.g., Reference 23),and also wound-directed filtered airflow studies. (See, e.g., Reference24).

Studies of surgical wound irradiation with conventional germicidal UVlamps have shown significant promise, with UV fluences, or doses,corresponding to about 4 to about 5 logs of methicillin-resistantStaphylococcus aureus (“MRSA”) cell kill, resulting in significantdecreases in SSI rates. For example, over a nineteen-year periodfollowing 5,980 joint replacements, the SSI rate without UV lighting,and with laminar airflow, was about 1.8%, and the infection rate with UVlighting was about 0.6%, a three-fold reduction (e.g., p<0.0001). (See,e.g., Reference 23). The downside of this approach, however, asmentioned above, can be that conventional germicidal UV lamps can be ahealth hazard to both patient and surgical staff, necessitating the useof cumbersome protective clothing, hoods and eye shields for thesurgical staff and the patient (see, e.g., References 25 and 26). Thus,there has been limited widespread use of germicidal UV lamps for woundsterilizing during surgery.

However, about 207 nm UV radiation can be as efficient as conventionalgermicidal lamps for inactivating MRSA, but can be far safer in regardto human exposure. Thus a continuous low-fluence-rate exposure of about207-nm UV radiation onto the surgical wound area during the entiresurgical procedure can be a safe approach to killing bacteria, as theyare alighted onto the wound area, and before they penetrated into theinterior of the wound—again potentially with no adverse effects onpatient or staff.

Considerable resources have been devoted to minimizing SSI rates, withonly moderate success, but one fundamental unresolved issue can be thatof drug-resistant bacteria such as MRSA. (See, e.g., Reference 27). Theuse of UV radiation directly addresses the issue of drug resistancebecause UV radiation can generally be equi-effective at inactivatingdrug-resistant bacteria compared with wild-type strains (see, e.g.,References 2 and 3)—and in fact all exemplary studies have beenperformed with MRSA—a drug resistant bacterial strain.

In practice, several 207-nm excimer lamps in a surgical setting can beused. The exemplary system, method and computer-accessible medium,according to an exemplary embodiment of the present disclosure, can beincorporated into a standard overhead surgical illumination system. Apossible second UV radiation source, to ensure a level of redundancyfrom inadvertent shielding, can be incorporated into a surgeon'sheadlight illumination system, with the UV radiation transmitted to theheadlight via fiber optics. (See, e.g., Reference 28).

Exemplary Reduction of Transmission of Influenza

In the United States, influenza results in about 3 million hospitaldays, and about $10 billion in health care costs—with the affectedpopulations largely the elderly and the very young. (See, e.g.,Reference 29). Influenza can spread rapidly, and the development ofvaccines can take months to accomplish. There can also be significantconcern about the pandemic spread of virulent strains of influenza suchas H5N1. Thus, effective methodologies to prevent the transmission ofinfluenza can be urgently needed. While it can be unlikely to be theonly route, airborne transmission of influenza via small aerosols cangenerally be considered the dominant person-to-person transmissionpathway, based on laboratory (see, e.g., References 30 and 31) andepidemiological studies. (See, e.g., References 32 and 33).

One exemplary approach that has been considered, and has shownconsiderable promise, can be irradiation of circulating room air with agermicidal UV lamp located in the upper part of the room—upper-room UVgermicidal irradiation (“UVGI”). (See, e.g., Reference 34). Whileclearly showing promise, due to their carcinogenic and cataractogenicpotential, the large-scale use of upper-room UV germicidal lamps has notbeen widely adopted. Specifically, in order to minimize UV radiationreaching individuals in the lower part of the room, modern UVGI fixturesuse louvers to collimate the UV beam away from the lower room. (See,e.g., Reference 35). However, while the louvers facilitate the UVGIsystems to meet the recommended limits for germicidal UV exposure, theyachieve this by blocking more than 95% of the UV radiation exiting theUVGI fixture, resulting in decreased effectiveness. (See, e.g.,Reference 36). A further consideration includes reports of accidentalgermicidal UVC exposure after incorrect UVGI usage. (See, e.g.,Reference 37).

Thus, the exemplary system, method and computer-accessible medium,according to an exemplary embodiment of the present disclosure, canreplace standard germicidal lamps within UVGI fixtures. Based on theexemplary data with H1N1 influenza virus, about 222 nm UV radiation canbe at least as effective, and potentially more effective, at killinginfluenza virus, as compared with conventional germicidal UV lamps, butit would not be subject to the human safety concerns. This would open upwidespread use of the exemplary system, method and computer-accessiblemedium in hospitals and communal settings.

Exemplary Anti-Microbial Applications

There can be many other scenarios in which airborne microbialtransmission can be a concern, which have the potential to beeffectively addressed using the exemplary system, method andcomputer-accessible medium. One bacterial example can be minimizingtuberculosis transmission, and the use of upper room UV germicidalirradiation has been shown to have significant potential in this regard(see, e.g., Reference 38), but with the safety caveats discussed above.With regard to viruses, use of the exemplary system, method andcomputer-accessible medium in airliners, hospitals, and other communitysettings can help limit pandemics such as SARS. A recent potentialapplication can be illumination in the personal protective equipment(“PPE”) removal room used by health care providers potentially exposedto infectious agents such as Ebola virus—which are known to be sensitiveto UV. (See, e.g., Reference 39). It has been widely suggested thatremoval/doffing of PPE can be a weak link in the systematic protectionof health care providers exposed to infectious agents. (See, e.g.,Reference 40).

The exemplary antimicrobial system/method can use, for example, on about207 nm or on about 222 nm single-wavelength UVC radiation (e.g., or anysource with the wavelengths in between) which can kill bacteria orviruses without damaging mammalian cells or tissues. (See, e.g.,Reference 1). The exemplary system, method and computer-accessiblemedium can differ significantly from using conventional mercury-basedgermicidal lamps which emit a dominant bactericidal wavelength at about254 nm, and which can be hazardous to humans. (See, e.g., References 26and 41-44).

Thus, the exemplary system, method and computer-accessible medium,according to an exemplary embodiment of the present disclosure, caninclude the production of UV wavelengths around 207 nm or around 222 nm,which can be equally toxic to bacteria/viruses as compared withconventional UV germicidal lamps, but can be far safer in terms of humanexposure.

Exemplary Development of a Monochromatic 207 nm UV Radiation Source

Excimer lamps (e.g., excilamps) can be an efficient source of nearmonoenergetic UV radiation (see, e.g., Reference 11), and with anappropriate gas mixture (e.g., in the exemplary case Kr+Br) produce anear monoenergetic 207 nm UV radiation source. FIG. 10 shows measuredspectra emitted from the exemplary KrBr excilamp. (See, e.g., Reference1). Excilamps, however, can emit significant fluences of higherwavelength light (see, e.g., graph shown in FIG. 10), and thesehigh-wavelengths can be more penetrating, which can result insignificant biological damage. Therefore, a customized bandpass filtercan be used to remove all but the dominant wavelength emission (see,e.g., FIG. 10 inset graph). The filtered excilamp, and a shutter, can beintegrated into a portable apparatus with a user-friendly stand. All theexemplary studies reported here were performed with these exemplaryfiltered excilamps. A typical geometry can produce a uniform powerdensity within about a 580 mm-diameter circular field at about 1-m lampdistance, with a power density of about 0.1 mW/cm².

Exemplary In Vitro Studies of Safety and Efficacy, Using HumanFibroblasts (Safety) and MRSA (Efficacy)

The exemplary experiments were performed in-vitro using human skinAG1522 fibroblasts, and with MRSA bacteria. Both the fibroblasts and theMRSA were irradiated unshielded on a surface. Cell survival was comparedwith a conventional germicidal lamp vs. the exemplary filtered 207 nmlamp. As shown in the graphs of FIGS. 11A and 111B, a 207 nm UV exposureproduces far less cell killing in human cells than a conventionalgermicidal lamp (e.g., FIG. 11A, curve 1105 illustrating the MRSA killsof a germicidal lamp and curve 1110 illustrating the human cell killsfor the germicidal lamp). At relevant fluences, 207-nm UV radiationkills MRSA almost as efficiently as a conventional germicidal lamp(e.g., FIG. 11B, curve 1115 illustrating MRSA kills for the exemplarysystem, method and computer-accessible medium and curve 1120illustrating human cell kills for the exemplary system, method andcomputer-accessible medium). For example, for the same level of MRSAkilling, the exemplary system, method, and computer-accessible mediumproduces about 1,000-fold less killing in human cells compared to aconventional germicidal lamp. (See, e.g., Reference 1).

Exemplary Safety Studies in a Human Skin Model

The exemplary on-surface in-vitro safety studies were extended by usinga full 3-D human skin model (e.g., EpiDerm, MatTek Corp), whichrecapitulates the human stratum corneum, epidermis and dermis). The skinmodel was irradiated from the top with UV radiation from a standardgermicidal lamp and with about a 207 nm UV-wavelength.Immunohistological performed assays for common premutagenic skinphotoproducts associated with UV exposure (e.g., cyclobutane pyrimidinedimers (“CPD”) and pyrimidine-pyrimidone 6-4 photoproducts (e.g., 6-4PP). The results are shown in the graph of FIG. 4. In contrast to theresults using a standard germicidal UV lamp, 207 nm UV radiationproduced essentially none of the photoproducts which can be associatedwith UV-related skin cancer.

Exemplary In-Vivo Safety Studies in Hairless Mouse Skin

The typical thickness of the SKH-1 hairless mouse stratum corneum can beabout 5 μm. (See, e.g., Reference 50). Thus, it can be a usefulconservative model for human skin, which has a typical range of stratumcorneum thicknesses from about 5 to 20 μm. (See, e.g., Reference 9).

Irradiation details are given below, where more extensive safety studiesusing the exemplary system, method, and computer-accessible medium areshown. Here, a group of 4 SKH-1 hairless mice was exposed to excilamp ata fluence of 150 mJ/cm², a second group of four 4 mice was exposed tothe same UV fluence from a standard UV germicidal lamp, and a thirdgroup of 4 mice received no (e.g., sham) UV radiation exposure.

At 48 hours post-exposure, the mice were sacrificed, and dorsal skinsections were prepared for analysis. The epidermal thickness wasassessed, as well as induction of cyclobutane pyrimidine dimers (“CPD”),and induction of pyrimidine-pyrimidone 6-4 photoproducts (e.g., 6-4 PP).

FIG. 12A shows an exemplary graph illustrating the effect of aconventional germicidal UV lamp 1205 and an exemplary filtered 207 nm UVlamp 1210 on the production of cyclobutane pyrimidine dimer in humanskin model. FIG. 12B shows an exemplary graph illustrating the effect ofa conventional germicidal UV lamp 1205 and an exemplary filtered 207 nmUV lamp 1210 on the production of pyrimidine-pyrimidone 6-4photoproducts (e.g., 6-4 PP) in human skin model.

FIG. 13A (e.g., top row) shows cross-sectional images of H&E stainedskin samples from the three mouse groups. The epidermal layer thicknessof the dorsal skin of the mice exposed to 150 mJ/cm² UV generated by theabout 207 nm or the about 222 nm lamp was not statistically differentfrom controls. By contrast, the same fluence generated by the about 254nm conventional germicidal lamp resulted in a 2.7±0.4 fold increase inepidermal thickness.

FIG. 13A (e.g., middle and lower rows) shows typical cross-sectionalimages of skin samples from the three groups comparing pre-mutagenicphotoproduct lesions CPD (e.g., middle row, dark stained cells) and 6-4PP (e.g., bottom row, dark stained cells). As expected, and as shown inFIG. 13A, exposure to 150 mJ/cm² from the 254-nm conventional germicidallamp resulted in a dramatic increase versus controls in the percentageof these lesions in epidermal cells, whereas the tissue exposed to thesame fluence of 207 nm UV radiation showed no statistically significanceincrease of these epidermal lesions relative to the controls. FIG. 13Bshows an exemplary chart illustrating a percent of epidermal cells withpremutagenic lesions for particular UV wavelengths for CPD (e.g., Sham1305, 254 nm 1310 and 207 nm 1315) and 6-4PP (e.g., Sham 1320, 254 nm1325 and 207 nm 1330).

Exemplary Optimizing MRSA Concentrations for Efficacy Studies in Pigs

Preliminary results from pig experiments designed to assess theappropriate initial concentration of MRSA were generated. In theexemplary experiments which did not involve UV irradiation, MRSA wasspread over the appropriate dorsal area of three pigs at different MRSAconcentrations (e.g., 105-107 cfu/ml). 12 superficial wounds weregenerated at each concentration, and the animals were observed for 7days, with the goal of finding the minimum MRSA concentration to producea 90% wound infection rate. Biopsy samples were also taken from allwounds at 7 days to confirm the source of the infection, and assayedusing serial dilution. Based on the wound infection numbers, 10⁷ cfu/mlwas chosen as the initial MRSA concentration (e.g., 11/12 woundsinfected), and for this concentration, the results from the biopsysamples averaged 1.5±1.0×10⁶ MRSA cfu/tissue sample. The bacterialcolonies appeared to be pure MRSA.

Exemplary Optimizing Efficacy Studies for Influenza Virus Inactivation

A standard plaque assay was optimized, and used to measure thefractional survival of H1N1 influenza virus after UV exposure. After thevirus was irradiated on a surface, the exemplary fractional survival(“S”) results were fitted, both for the 207 nm UV radiation exposure andfor the conventional germicidal lamp exposure, to the standard (see,e.g., Reference 29) exponential model, S=exp(−Z), where there can be aUV fluence and Z can be the so called “susceptibility” parameter. From aconventional germicidal lamp plaque forming unit (“PFU”) data, asusceptibility parameter value of Z=0.32 m²/J was derived; a range thathas been previously used. (See, e.g., Reference 29). From the 207 nmdata, a susceptibility parameter value of Z=0.42 m²/J was derived,suggesting that 207 nm UV radiation can be even more effective thanconventional germicidal lamps for inactivating H1N1 influenza virus.

Exemplary Design, Construction and Use of a Bench Top Aerosol UVExposure Chamber

A bench top aerosol exposure chamber was designed and constructed, whichis shown in the image in FIG. 14. The Aerosol Generation Module 1405 hassaturated/desiccated air and collision-nebulizer inputs, and has aseries of internal baffles for droplet distribution. Temperature andhumidity meters can monitor the conditions in the aerosol generationchamber, after which the aerosols can be flowed through the UV-exposuremodule which has a 300×275 mm silica Quartz Window 1410 on the UVirradiator side, and a quartz port on the far side to monitor UVirradiance with a UVC radiation meter. The aerosols can be in the UVfield for times depending on the flow rate, which in turn can determinethe UV radiation dose, and which can also be adjusted by moving the lampnearer or further from the window. A particle sizer can measure sizedistribution of the aerosols in the UV irradiation volume. The aerosolscan be drawn through output ports to two BioSamplers in the SamplingModule 1415.

86.9% of the aerosol was sized between 0.3 and 0.5 μm, 10.9% between 0.5and 0.7 μm, 1.9% between 0.7 and 1.0 μm, and 0.3% greater than 1 μm.These size distributions (e.g., at 37.9% relative humidity and 24.6 C)can be changed by changing the relative humidity, and can represent theappropriate aerosol size range for from human exhaled breath and coughs.(See, e.g., Reference 53 and, 54).

Exemplary Hairless Mouse Irradiation

As shown in the exemplary image provided in FIG. 15, Mice 1505 can beplaced individually in Compartments 1510 with size 60 mm (“W”), 125 mm(“L”) and 80 mm (“H”) in specially-designed mouse-irradiation boxes,where the Mice 1505 can be housed before (e.g., 48 hours acclimatizationtime), during, and after UV exposures, while being given water andPurina Laboratory Chow 5001 diet ad libitum. A metal-mesh top on themouse-irradiation box can facilitate UV radiation transmission from theexemplary 207-nm KrBr excilamp or from a 254-nm germicidal lamp.

Various conditions can be used, which can include, for example: (i) shamexposure, (ii) 207-nm KrBr lamp at either 50 or 150 mJ/cm², and (iii)germicidal UV lamp at either 50 or 150 mJ/cm². A 207-nm UV excilampemission characteristics in-situ can be measured prior to mouseexposures using a UV Technik Micro Puck UV dosimeter and a PhotonControl UVC spectrometer.

A total of 245 SKH-1 hairless mice (e.g., 7 weeks old; strain code: 477;Charles River Labs) can be used to determine the effects from long-termUV radiation exposures. The total number of mice can be separated intotwo groups for 8 hours/day irradiations during 1 day and 1 month. Asshown in the diagram of FIG. 16, a 70 mice per exposure-duration groupcan be used (e.g., element 1605), with 105 additional mice (e.g., 1640)used for a time series (e.g., 1660) of immunohistochemical and molecularendpoints following the 1-day exposure

Each group of 70 mice (e.g., 1605) can be divided into two subgroupswhere 35 mice (e.g., 1625) can be harvested for assays (e.g., TissueSection 1660) following the exposures and the other 35 mice (e.g., 1610)can undergo live assays of skin properties (e.g., 1615) and then can bemaintained for an additional 9 months for eye studies (e.g., 1620). Eachgroup of 35 mice can contain mice representing each of the exemplaryexposure conditions: (i) sham exposure, (ii) 207-nm KrBr lamp at either50 or 150 mJ/cm² and (iii) germicidal UV lamp at either 50 or 150mJ/cm².

Exemplary Pig Skin Irradiations

The exemplary porcine model can be exposed to various exposureconditions, which can include, for example: (i) sham exposure, (ii)207-nm KrBr lamp at either 50 or 150 mJ/cm² and, (iii) germicidal UVlamp at either 50 or 150 mJ/cm². UV radiation exposure times can be inthe range of about 20 minutes to 1 hour. Two pigs, one male and onefemale, can be used and all exposure conditions can be delivered to eachanimal, because the dorsal surface area on a pig can be sufficient formultiple acute exposure conditions and can provide multiple tissuesamples. Each pig can be anesthetized during the exposures and eachexposure condition can be delivered to a predetermined dorsal region ofthe animal. Following the acute exposures, skin properties can berecorded and tissue samples can be collected via skin punch forbiological assays at 0, 24, 48 and 72 hours, to parallel the mouse skinirradiation experiment.

Exemplary Biological Assays for Mouse and Pig Safety Studies SkinProperties Assays

The exemplary live assays can focus on skin properties. (See, e.g.,References 58 and 59). Skin erythema can be assessed by comparing skinredness measurements (see, e.g., Reference 60) before andpost-irradiation using an exemplary Konica-Minolta handheld colorimeter(e.g., Chroma Meter CR-410T) currently being used to quantitate humanskin erythema in radiotherapy patients. Skin trans-epidermal water losscan also be measured using a ServoMed Evaporimeter EP-2. All mice usedin the live assays can be maintained for an additional 9 months for theexemplary mouse eye studies described below.

Exemplary Tissue Sections Assays

Dorsal skin tissue sections were harvested from sacrificed mice and fromlive pig for skin imaging, immunohistochemical and molecular endpoints.For the exemplary skin-imaging endpoint, tissue-section assays wereharvested from mice and from pig skin punches. Confocal and multi-photonmicroscopy procedures were used along with advanced image analysistechniques (e.g., Velocity, Metamorph), available at the AdvancedImaging Core in the Skin Disease Research Center at Columbia University,to examine microscopic features of the fixed skin and to measureskin-layer thicknesses. For the 1 month exposures, the exemplaryskin-imaging endpoint assays were applied on tissue sections harvestedfrom mice immediately following the exposures. For the exemplary 1-day(e.g., 8-h) exposure duration, the mice were sacrificed at 72 hours, atime point reported for maximal edema following UVB exposure. (See,e.g., Reference 58).

For the exemplary immunohistochemical and molecular endpoints, tissuesections were assayed using the Tissue Culture & Histology Core at theSkin Disease Research Center, Columbia University Medical Center. A timeseries (e.g., 1660) was used following the exemplary 1-day (e.g., 8-h)exposure with samples harvested at 0 hours (e.g., 1645), 24 hours (e.g.,1650), 48 hours (e.g., 1655) and 72 hours (e.g., 1635) (note: 72-hsamples acquired from mice used in the skin-imaging endpoint—see above).Specifically, fixed skin tissue sections were stained with hematoxylinand eosin for histological analysis. The induction of DNA photodamage,inflammation and apoptosis was examined. DNA photodamage were detectedby immunohistochemical analysis of cyclobutane pyrimidine dimers and 6,4-photoproducts in fixed tissues. These procedures illustrateinflammatory cell infiltration of either lymphoid or myeloid origin.Inflammatory responses were further investigated using markers for mastcells and macrophages. Similarly, apoptosis were assessed with the TUNELassay and/or the immunohistochemistry-based Caspase-3 activationanalysis. Alteration in cutaneous vasculature as well as early onset offibrosis was investigated. UV-induced alterations in cutaneousvasculature were examined through endothelial markers such as CD 31,whereas markers for collagen and elastin fibers formation were used toobserve potential early onset of fibrosis.

Exemplary Mouse Eye Assays

Ultraviolet irradiation of the eye can be associated with a variety ofocular disorders including eyelid and conjunctival abnormalities,corneal pathologies and cataract. (See, e.g., References 61-64). Theseverity and type of pathology can be related to both dose and UVwavelength. Pathologies can arise from direct action of UV radiation,for example, cyclobutane-pyrimidine dimer formation leading tomutagenesis (see, e.g., References 5, 65 and 66), or indirectly by freeradical mediated photochemical interactions with intraocular fluids andsub-cellular components. (See, e.g., References 67-69).

These endpoints can be measured morphologically by weekly slit lampexamination of the anterior segment. While it can be unlikely that UVradiation of this wavelength can result in cataract due to theapproximately 295 nm UV cutoff of the cornea (see, e.g., References 72and 73), to rule out UV-induced lens changes, dilated slit lamp examscan be performed periodically. Potential corneal, conjunctival and lenschanges can be scored as to severity using generally accepted subjectivecriteria (see, e.g., References 64, 74 and 75) and slit lampphotodocumentation.

UV-induced anterior segment changes can also be analyzed histologicallyin selected animals sacrificed at weekly intervals followingirradiation. Paraffin fixed and stained horizontal sections of the eyeand orbit can be prepared and analyzed for abnormalities. (See, e.g.,References 64, 76 and 77).

To determine the potential effects of irradiation on visual disability,Virtual Optomotor System (“VOS”) contrast sensitivity testing can beemployed. (See, e.g., Reference 78). VOS can be a simple, precise andrapid method of quantifying mouse vision that permits reliable trackingof both onset and progression of decrements in visual acuity andcontrast sensitivity. (See, e.g., Reference 79). Acuity can be reliablyquantitated by varying the spatial frequency of a displayed variablevertical sine wave grating until an optomotor (e.g., head turning)response was no longer elicited by the subject animal. The advantage ofthis approach can be that it can permit direct measurement of visualfunction rather than more subjective estimates of the effect of ocularchanges on acuity. In all cases, data can be analyzed to determinebaseline increases in prevalence, incidence or rate of progression ofirradiation specific ocular pathologies.

Exemplary Statistical Considerations

The same, or similar, statistical analysis can be applied to the mousestudies and the pig studies—although smaller pig numbers can be usedthan mice, because multiple regions of the pig dorsal skin can besubject to different exposure conditions, whereas each mouse can beexposed to only one exposure condition.

Analysis of variance (“ANOVA”) can be used to analyze the data from theseries of experiments performed to address this aim, using statisticalcriteria of about 80% power (e.g., beta=0.2) and about 95% significance(2*alpha=0.05). For example, for the live assays of skin properties,skin imaging and eye studies, the sample size of 70 mice divided into 5groups were sufficient to detect effect sizes of 0.4 or more for theresponse variables.

For the time series of immunohistochemical and molecular endpoints, theproposed sample size of 140 mice divided into 5 groups, with repeatedmeasurements at 4 time points, can warrant the use of multivariateanalysis of variance (“MANOVA”). This sample size can be sufficient todetect effect sizes of about 0.2 or more for the response variables.

Exemplary Efficacy Studies for MRSA Killing in Mouse Skin and Pig Skin

A liquid suspension containing live MRSA was applied to the skin on theback of the SKH-1 hairless mouse and the pigs, followed by woundinduction and suturing. One set of wounds was treated with topicalantibiotics (e.g., positive control), another set was untreated (e.g.,negative control), and a third set was exposed to 207 nm radiation.Staged inspections of wounds for infection were undertaken usingobjective wound assessment criteria.

207 nm radiation can be effective in killing bacteria while potentiallybeing much safer than conventional germicidal lamps for human exposure.The exemplary application to minimizing SSI rates can involve 207-nmirradiation of the wound during surgery to inactivate airborne bacteriaas they can alight onto the wound. The exemplary proposed in-vivostudies using 207 nm irradiation of hairless mouse and pig models can bedesigned to provide a first assessment of the efficacy of the exemplarysystem, method and computer-accessible medium for killing bacteriaand/or viruses, which can be introduced onto the skin surface, in thecontext of surgical wounds. The exemplary endpoints can be prevention ofwound infections.

Exemplary In-Vivo Hairless Mouse Skin Model

The efficacy of 207 nm UV radiation in preventing infections atpredetermined concentrations of MRSA can be determined. SKH-1 hairlessmice were anesthetized with isoflurane, and after cleaning with alcoholand povidone-iodine solution, a 20 mm×20 mm area were marked on thedorsal skin. The MRSA solution at the previously determinedconcentration was applied to the marked area and allowed to dry. Asubset of the mice was exposed to the 207 nm lamp to a total fluence of50 mJ/cm² or 150 mJ/cm², with the remaining mice serving as positivecontrols. Mice not inoculated with MRSA, but treated with the lamp, wererun in parallel to serve as negative controls. A 10 mm incision was madewithin the 20 mm×20 mm region of each mouse through the skin andepidermis. Incisions were closed using wound clips.

72 mice, and thus 72 wounds, were used, the same as planned for the pigskin studies described below (e.g., 24 mice receiving either 50 or 150mJ/cm²; 24 mice receiving topical antibiotic; 24 mice receiving notreatment). Power calculations are described below.

The mice were housed individually in custom designed boxes (see, e.g.,FIG. 7) and were monitored daily for infection of the wound (e.g., asseen by erythema and purulent drainage) for up to 7 days. Mice withinfected wounds were immediately euthanized and the wounds processed, asdescribed below. At day 7, mice were euthanized with CO₂ and cervicaldislocation. Infected wounds were further assayed for inflammation andbacteria culture. A 2 mm punch biopsy section of each wound wasprocessed for bacterial culture while the remainder was fixed in 10% NBSfor assessed of inflammation. The degree of inflammation was graded on ascale of 0 to 3 (see, e.g., Reference 81), while biopsy sections wereassayed for bacteria titers using the CFU assay.

Exemplary In-Vivo Porcine Skin Model

Pig skin offers an excellent model from the perspective of dermatologyand wound investigation. (See, e.g., Reference 56). A multitude ofmorphologic, anatomic, immunohistochemical, dermatologic andpharmacologic studies have demonstrated that pig skin has importantsimilarities in morphology, cellular composition and immunoreactivity tohuman skin. (See, e.g., References 82 and 85).

The exemplary pig-skin wound studies were divided into two phases. PhaseI was the design optimization phase, to assess the appropriateconcentration of MRSA for the exemplary Phase II studies, and tooptimize the exemplary assay protocols. In these exemplary Phase Istudies, which do not involve UV irradiation, after the wound infectionprocedure, tissue biopsy samples were suspended in trypticase soy broth,sonicated, and serially diluted on TSA plates. MRSA colony counts weredetermined after incubating the plates at 37° C. for 36 hours. From thePhase I trial using an initial 107 cfu/ml for contamination, theexemplary results from 12 biopsy samples averaged about 1.5±1.0×106 MRSAcfu/tissue sample, indicating that 107 cfu/ml was an appropriate initialMRSA concentration for the exemplary first UV studies.

Phase II studies, involved superficial (e.g., skin/subcutaneous) woundsin 6 pigs. A range of 207-nm fluences was used, and a follow-up time of7 days used to assess wound infection rates.

The exemplary studies can use pathogen free domestic pigs weighingapproximately 22-25 kg and involved, for example:

-   -   1) Shaving, cleaning and preparing skin on the pig's back;    -   2) Topical application of a solution containing appropriate        concentrations of MRSA bacteria onto the skin;    -   3) Exposing the skin bearing the MRSA to 207 nm UV radiation or,        as a positive control, to a standard topical antimicrobial        agent;    -   4) Creating a series of superficial wounds on the pig skin,        under anesthesia;    -   5) Closing and individually covering the wounds with Dermabond        liquid skin adhesive;    -   6) Visually monitoring the wounds daily for infection over the        observation period;    -   7) If an individual wound can be visually determined to be        infected, the Dermabond can be removed, the infected wound        swabbed with a culture stick, and the sample transferred to        standard tubed media for culturing, after which Dermabond can be        reapplied to the wound;    -   8) At the end of the observation period, after humane sacrifice,        all wounds were swabbed and biopsied to measure bacterial        concentration.

Exemplary Porcine Study: 207-nm Irradiation and Controls

The MRSA concentration was, for example, 10⁷ cfu/ml. Each pig wasoptically masked to define the region were be exposed to 207-nm UVradiation. While each pig received only one single 207 nm fluence, theindividual 207 nm fluences applied to all the pigs, and ranged fromabout 50 to about 150 mJ/cm². Positive control wounds received povidoneiodine (e.g., betadine), a well characterized bactericidal agent (see,e.g., References 86 and 87), and negative controls involved neither UVradiation nor topical antimicrobial agent.

Exemplary Porcine Study: Surgical Wounds

A total of 12 wounds per pig, 60 mm long, and separated by a minimum of25 mm were used. In each pig, 4 wounds were in the 207-nm UV-irradiatedregion, 4 wounds were subject to the topical antimicrobial agent and 4wounds acted as controls. The wounds were closed using absorbablesutures and then individually covered with Dermabond. Wounds were closedusing 4-0 Biosyn.

Exemplary Porcine Study: Infection Monitoring

Every wound was visually monitored daily for signs of infection. If anindividual wound was visually determined to be infected, the Dermabondwas removed, the infected wound swabbed with a culture stick, and thesample transferred to standard tubed media for culture, after whichDermabond was reapplied to the wound. At the end of the 7 dayobservation period, the animals were humanely sacrificed and all woundswere both swabbed and biopsied to measure bacterial concentration.

Exemplary MRSA Efficacy Studies: Statistical Power Considerations

Power calculations apply to both the mouse and the pig studies, as thesame number of wounds (see, e.g., Reference 72) can be planned for both.A logistic regression was used to model the relationship betweeninfection control probability and UV dose. There were 24 controlincisions (e.g., receiving zero UV radiation dose), 12 incisions withthe low UV radiation dose (e.g., 50 mJ/cm²), and 12 with the high UVradiation dose (e.g., 150 mJ/cm²). Using criteria of 80% power (e.g.,beta=0.2) and 95% significance (e.g., 2*alpha=0.05), these sample sizeswere sufficient to detect a dose response which can extend from about10% wound control probability at zero UV dose up to about 99% woundcontrol probability at the high UV dose.

Exemplary UV Inactivation of Influenza Virus

The exemplary studies utilized a frozen suspension of H1N1 influenzaviruses (e.g., A/PR/8/34 H1N1; ATCC VR-95, Manassas, Va.). The virussuspension was thawed and divided into single-use aliquots to berefrozen and stored at −80° C. until needed. An optimized plaque assaywas used to measure virus titer before and after UV irradiation.

The exemplary protocols were optimized for the surface based viralinactivation studies. In the exemplary surface virus study 50 μL ofinfluenza virus suspension was seeded from a titer of approximately 109focus forming units/ml, onto 25 mm×75 mm substrates that simulatestypical surfaces found within workspaces and operating rooms: stainlesssteel, glass and plastics. The deposited liquid evaporated during adrying time of approximately 20 min, depending on ambient conditions.The exemplary control-seeded substrates were continually exposed toambient conditions inside a biological safety cabinet. The remainingseeded substrates (e.g., along with a clean substrate used as a negativecontrol) were placed in the exemplary 207 nm or 222 nm exposure chamber,designed and built in-house at the exemplary instrument shop. All viruswork was performed in a BSL-2 biological safety cabinet.

Seeded substrates were divided into two sets for UV radiation treatment;one set was treated using a KrBr excilamp (e.g., 207 nm) and the otherset received comparable exposures using conventional germicidal lamps toprovide positive controls. Groups of 3 seeded substrates were removedfrom the exposure chamber after each 207 nm exposure. Exposure dosesranged from between about 50 and about 150 mJ/cm². The control-seededsubstrates were sham irradiated. Immediately after the last 3 seededsubstrates were removed from the exposure chamber; each seeded substratewas washed with DPBS++(e.g., DPBS [1×]+Mg++ and Ca++) using thefollowing procedure. A clearly-marked portion of the seeded substratewhere viruses was deposited can be washed 10 times with a single 900-μLvolume of DPBS++, using a pipette to remove all residue. The virusplaque assay was performed on the DPBS++ volume that was used to washeach seeded substrate.

Exemplary Virus Plaque Assay

Viral infectivity was assessed with the standard plaque assay (see,e.g., Reference 91), which was optimized. Immediately after exposure ofinfluenza A virus (e.g., H1N1; A/PR/8/34) to UV radiation, confluentMadin-Darby Canine Kidney Epithelial cells (e.g., MDCK; ATCC CCL-34) wasincubated for 1.5 hours with serial dilutions of the virus. The viruswas aspirated and the cells overlaid with 0.6% Avicel (see, e.g.,Reference 92) in medium (e.g., 2×MEM/BSA) containing TPCK-trypsin tofinal concentration of 2.0 μg/ml. Plates were incubated at 37° C. for atleast 3 days. Viral infectivity was expressed as plaque-forming units,PFU/ml.

Exemplary Influenza Virus in Aerosol Studies

While there can be numerous modes of influenza transmission, the spreadof influenza virus via aerosols can be a key route (see, e.g., Reference93); with the majority of expiratory aerosols in the submicron sizerange. (See, e.g., Reference 53). While distinct physiological processescan be responsible for aerosols with specific size distribution modes,the majority of particles for all activities can be produced in one ormore modes with diameters below approximately 0.8 μm. (See, e.g.,Reference 54).

Exemplary Bench Top Aerosol UV Exposure Chamber

The aerosol studies were performed in a BSL-2 cabinet using theexemplary bench top UV aerosol exposure chamber. (See, e.g., FIG. 6there). In the exemplary preliminary aerosol studies with the exemplaryaerosol chamber, 86.9% were sized between 0.3 and 0.5 μm, 10.9% between0.5 and 0.7 μm, 1.9% between 0.7 and 1.0 μm and 0.3% greater than 1 μm.These size distributions were changed by changing the input air/aerosolratio.

Influenza aerosols were generated by adding 0.075 ml of undilutedinfluenza virus and 75 ml of buffer (e.g., Dulbecco's phosphate-bufferedsaline with calcium and magnesium containing 0.1% bovine serum albumin)into a high-output extended aerosol respiratory therapy (“HEART”)nebulizer (e.g., Westmed, Tucson, Ariz.) pressurized at 69 kPa. Toachieve a particular relative humidity, the nebulizer output was mixedwith proportions of dry and humidified air in a 7.5-liter chamber priorto delivery to the aerosol exposure chamber. Relative humidity (“RH”)and temperature in the chamber were measured prior to the exposuresection using an Omega RH32 temperature and relative humidity meter(e.g., Omega Engineering Inc., Stamford, Conn.).

The exemplary KrBr 207-nm excilamp exposures were used to deliver UVradiation sterilization treatments and a standard germicidal UVradiation lamp for positive controls. During exposures, the UVCirradiance was monitored using a UVC radiation meter detecting UVCradiation transmitted through a fused quartz port opposing the UVCradiation entrance port at the exposure section of the chamber. Exposuredoses ranged up to about 150 mJ/cm², which spans dose levels used inprevious studies using standard germicidal lamps to inactivate influenzavirus. (See, e.g., Reference 29). The UVC radiation dose was computed bymultiplying the UVC irradiance by the exposure time. The exposure timewas computed by dividing the volume of the chamber by the airflow rate.Based on the exemplary design dimensions and the exemplary plannedairflow rate, an exposure time of approximately 8 seconds was expected.

Air can be drawn through the chamber by a pump at 25 liters/minutethrough a manifold attached to 2 SKC Biosamplers (e.g., SKC Inc., EightyFour, Pa.), each operating at 12.5 liters/minute. Each Biosamplercontains 20 ml of virus buffer (e.g., Dulbecco's phosphate-bufferedsaline with calcium and magnesium containing 0.1% bovine serum albumin).A HEPA filter was placed after the samplers to remove fugitive aerosolsbefore the airstream enters the pump. When sampling was not in progress,the aerosol-laden airstream running through the chamber were bypassedaround the samplers, and the 25-liter/minute flow was directed to theHEPA filter.

Exemplary Aerosol Studies: Experimental Protocol

The nebulizer was run for about 20 minutes before sampling to ensurethat concentrations within the chamber have stabilized. Samples werecollected by passing the entire chamber airflow through the Biosamplersfor a period of about 15 minutes. Sample sets were collected thatconsist of samples with: (i) the 207-nm KrBr excilamp on, (ii) the254-nm germicidal lamp on (e.g., for positive controls), and (iii) withthe UV radiation off (e.g., for negative controls). Triplicate samplesets were collected for combinations of the UVC radiation dose (e.g.,ranging up to about 150 mJ/cm²) and RH (e.g., about 25%, about 50% andabout 75%). After each sampling, the BioSamplers were removed from thechamber, the volume of collection liquid was measured, and viruscollection fluid was stored at 4° C. for a maximum of 3 hours prior toperforming the infectivity assay. The BioSamplers was decontaminatedwith about 10% bleach, rinsed with about 70% ethanol and dried beforereusing.

Exemplary Survival Results for H1N1

For example, 100 μl of influenza A viral suspension (e.g., H1N1;A/PR/8/34) in phenol-free Hank's Balanced Salt Solution with calcium andmagnesium (e.g., “HBSS⁺⁺”) was spread onto a 30-mm Petri dishes andimmediately exposed to either a UVC light generated by a KrCl lamp(e.g., at about 222 nm) or by a conventional mercury germicidal lamp at254 nm. 900 μl of HBSS⁺⁺ was then used to collect the exposed viralsuspension, and was serially diluted for infectivity assay on confluentMadin-Darby canine kidney (“MDCK”) cells. Cells were infected with thevirus for about 45 minutes. The cells were then washed and incubatedovernight. A fluorescent-focus reduction assay (see, e.g., Reference 95)was performed to assess the viral infectivity. The number of cellsshowing fluorescent foci (e.g., fluorescent focus units (“FFU”)) wascomputed based on dilution factors, and the ratio of FFU per samplerelative to control calculated. As shown in FIG. 17, the exemplaryresults indicate that the exemplary KrCl excilamp having a wavelength ofabout 222 nm (e.g., element 1705) can be as effective as a conventionalgermicidal UV lamp at 254 nm (e.g., element 1710) for killing InfluenzaA virus (e.g., H1N1; A/PR/8/34). Thus, while the KrCl excilamp at about222 nm can be as effective as a conventional germicidal UV lamp at 254nm, the KrCl lamp at 222 nm does not damage the surrounding tissue likethe conventional germicidal UV lamp does.

FIG. 18 shows an exemplary flow diagram of an exemplary method forselectively killing or affecting a virus according to an exemplaryembodiment of the present disclosure. For example, at procedure 1805,radiation can be provided having one or more wavelengths that can beconfigured to selectively harm or damage the virus on a surface or in anaerosol. Alternatively, or in addition, at procedure 1805, aparticularly sized volume of air having the virus therein can beirradiated using a radiation having one or more wavelengths that can bein a range of between about 200 nm and about 230 nm. At procedure 1810,a filter can be provided such that, at procedure 1815, the radiation canbe substantially prevented from having any wavelength that can besubstantially harmful to cells of the body (e.g., a wavelength that isoutside the range of between about 200 nm and about 230 nm).

The foregoing merely illustrates the principles of the disclosure.Various modifications and alterations to the described embodiments willbe apparent to those skilled in the art in view of the teachings herein.It will thus be appreciated that those skilled in the art will be ableto devise numerous systems, arrangements, and procedures which, althoughnot explicitly shown or described herein, embody the principles of thedisclosure and can be thus within the spirit and scope of thedisclosure. In addition, all publications and references referred toabove can be incorporated herein by reference in their entireties. Itshould be understood that the exemplary procedures described herein canbe stored on any computer accessible medium, including a hard drive,RAM, ROM, removable disks, CD-ROM, memory sticks, etc., and executed bya processing arrangement and/or computing arrangement which can beand/or include a hardware processors, microprocessor, mini, macro,mainframe, etc., including a plurality and/or combination thereof. Inaddition, certain terms used in the present disclosure, including thespecification, drawings and claims thereof, can be used synonymously incertain instances, including, but not limited to, for example, data andinformation. It should be understood that, while these words, and/orother words that can be synonymous to one another, can be usedsynonymously herein, that there can be instances when such words can beintended to not be used synonymously. Further, to the extent that theprior art knowledge has not been explicitly incorporated by referenceherein above, it can be explicitly incorporated herein in its entirety.All publications referenced can be incorporated herein by reference intheir entireties.

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The following references are hereby incorporated by reference in theirentirety.

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1. An apparatus for selectively killing or affecting at least one virus,comprising: a radiation source first arrangement configured to generateat least one radiation having one or more wavelengths in a range ofbetween about 200 nanometers (nm) to about 230 nm, wherein the at leastone radiation is configured to selectively harm or damage at least onevirus; and at least one filter second arrangement configured tosubstantially prevent the at least one radiation from having anywavelength above about 240 nm that is substantially harmful to cells ofa body.
 2. The apparatus of claim 1, wherein the at least one radiationis further configured to selectively affect or destroy at least onebacteria on the surface or in the aerosol.
 3. The apparatus of claim 1,wherein the radiation source includes an excilamp.
 4. The apparatus ofclaim 3, wherein the excilamp includes at least one of a krypton-brominelamp or a krypton-chlorine lamp.
 5. The apparatus of claim 1, whereinthe radiation source first arrangement is further configured to generatethe at least one radiation having a single wavelength, and wherein theat least one second arrangement is further configured to prevent the atleast one radiation from having any wavelength above about 240 nm otherthan the single wavelength.
 6. The apparatus of claim 5, wherein thesingle wavelength is about 207 nm.
 7. The apparatus of claim 5, whereinthe single wavelength is about 222 nm.
 8. The apparatus of claim 1,wherein the at least one second arrangement includes at least one of achemical filter or a dielectric.
 9. The apparatus of claim 1, whereinthe one or more wavelengths have a range of about 207 nm to about 222nm.
 10. The apparatus of claim 1, wherein the one or more wavelengthshave a range of about (i) 190-194 nm, (ii) 195-199 nm, (iii) 200-204 nm,(iv) 205-209 nm, (v) 210-214 nm, (vi) 215-218 nm, (vii) 219-223 nm, or(viii) 224-230 nm.
 11. The apparatus of claim 5, wherein the singlewavelength is at least one of (i) about 201 nm, (ii) about 202 nm, (iii)about 203 nm, (iv) about 204 nm, (v) about 205 nm, (vi) about 206 nm,(vii) about 208 nm, (viii) about 209 nm, (ix) about 210 nm, (x) about211 nm, (xi) about 212 nm, (xii) about 213 nm, or (xiii) about 214 nm.12. The apparatus of claim 5, wherein the single wavelength is at leastone of (i) about 215 nm, (ii) about 216 nm, (iii) about 217 nm, (iv)about 218 nm, (v) about 219 nm, (vi) about 220 nm, (vii) about 221 nm,(viii) about 223 nm, (ix) about 224 nm, (x) about 225 nm, (xi) about 226nm, (xii) about 227 nm, (xiii) about 228 nm, (xix) about 229 nm, or (xx)about 230 nm.
 13. The apparatus of claim 1, wherein the virus has asusceptibility parameter of Z=0.42 m²/J.
 14. The apparatus of claim 1,wherein the surface includes an animate surface.
 15. The apparatus ofclaim 14, wherein the animate surface includes at least one of (i) skinof at least one person, (ii) a cornea of the at least one person or(iii) mucous of the at least one person.
 16. The apparatus of claim 1,wherein the surface includes an inanimate surface.
 17. The apparatus ofclaim 16, wherein the inanimate surface includes at least one fomitesurface. 18-43. (canceled)